Rationale: Acute stress has been associated with changes in cognitive performance and mood, and these have been in part associated with stress-related increased release of cortisol. Both glucose and caffeine consumed in isolation have been shown to moderate cortisol response and affect cognitive performance and affect mood; however, there has been very little research into their behavioural and physiological effects when taken in combination. The aim of this study was to assess the effect of the two substances in combination under stressful and physically demanding conditions (fire-fighting training) on cognition, mood and cortisol release. Methods: Using a double-blind, mixed measures design, 81 participants were administered a 330-ml drink containing either (1) 50 g glucose and 40 mg caffeine, (2) 10.25 g of fructose/glucose and 80 mg caffeine or a placebo drink and tested across a range of cognitive tasks, mood and physiological measures. Results: The results showed an increase in grip strength and improved memory performance after ingestion of the drink containing 50 g glucose and 40 mg caffeine, and both active drinks resulted in improved performance on the information-processing task compared to the placebo. In terms of mood effects, the drink containing 50 g glucose and 40 mg caffeine led to a reduction in anxiety and significantly reduced self-reported levels of stress following the fire-fighter training. Conclusions: Based on the results of this study, in situations of stress combined with physical performance, administration of an energy drink containing glucose and caffeine might be an easy to implement and cost effective way to maintain mental performance levels and to ameliorate the negative effects of stress on mood.